Global Burden of Cancer

For many years, global health has been associated with diseases like HIV/AIDS and malaria. And rightly so. These diseases present significant threats to health around the world. But they aren't the only major killers. In fact, they're not even the leading killers anymore! Today, cancer claims more lives globally than HIV/AIDS, malaria, and tuberculosis combined, and the death toll from cancer is only going to grow.

Cancer is a major burden of disease worldwide. Each year, tens of millions of people are diagnosed with cancer around the world, and more than half of the patients eventually die from it. In many countries, cancer ranks the second most common cause of death following cardiovascular diseases.

Peter B. Bach, M.D., of the Memorial Sloan-Kettering Cancer Center, New York, and colleagues conducted a systematic review to examine the evidence regarding the benefits and harms of low-dose computerized tomography (LDCT) screening for lung cancer, which is the leading cause of cancer death. “Most patients are diagnosed with advanced disease, resulting in a very low 5-year survival rate,” the authors write. “Renewed enthusiasm for lung screening arose with the advent of LDCT imaging, which is able to identify smaller nodules than can chest radiographs.”

For the review, the researchers identified 8 randomized controlled trials and 13 cohort studies of LDCT screening that met criteria for inclusion. Three randomized studies provided evidence on the effect of LDCT screening on lung cancer mortality, of which the National Lung Screening Trial was the most informative, demonstrating that among 53,454 participants enrolled, screening resulted in significantly fewer lung cancer deaths (20 percent lower relative risk). The other 2 smaller studies showed no such benefit. “In terms of potential harms of LDCT screening, across all trials and cohorts, approximately 20 percent of individuals in each round of screening had positive results requiring some degree of follow-up, while approximately 1 percent had lung cancer. There was marked heterogeneity in this finding and in the frequency of follow-up investigations, biopsies, and percentage of surgical procedures performed in patients with benign lesions.” The authors write that “Low-dose computed tomography screening may benefit individuals at an increased risk for lung cancer, but uncertainty exists about the potential harms of screening and the generalizability of results.”

This report, a multisociety collaborative initiative, forms the basis of the American College of Chest Physicians and the American Society of Clinical Oncology clinical practice guideline, which, in summary is:

Recommendation 1: For smokers and former smokers ages 55 to 74 years who have smoked for 30 pack-years (number of packs of cigarettes smoked per day by the number of years the person has smoked) or more and either continue to smoke or have quit within the past 15 years, it is suggested that annual screening with LDCT should be offered over both annual screening with chest radiograph or no screening, but only in settings that can deliver the comprehensive care provided to National Lung Screening Trial participants. (Grade of evidence 2B, indicating a “weak recommendation based on moderate quality research data”)

Lung-Cancer Mortality and Low-Dose CT Screening
In a study published in this week’s NEJM, The National Lung Screening Trial Research Team report their findings on the efficacy of low-dose CT scans in reducing lung cancer mortality among high risk patients. Joe indeed is high-risk as defined by this study’s inclusion criteria: patients were between the age of 55 and 74, had to have at least a 30-pack year smoking history, and if former smokers, had quit within the last 15 years.

Over 50,000 patients who met these criteria were randomized and screened yearly by either CT or chest radiography for 3 years. They were then followed for 3.5 years with no screening. For the primary end point of lung cancer mortality, screening with low dose CT yielded a statistically significant reduction in lung cancer deaths, an absolute risk reduction of 20%. The authors estimate that there are 7 million such high-risk patients in the U.S., and an additional 94 million who are current or former smokers. Though 300 high-risk patients would need to be screened to prevent one death, these data suggest that one in five lung cancer deaths could be prevented.

Does this mean that we should be recommending screening for everyone who is at high risk? Not quite.

Recommendation 2: For individuals who have accumulated fewer than 30 pack-years of smoking or are either younger than 55 years or older than 74 years, or individuals who quit smoking more than 15 years ago, and for individuals with severe comorbidities that would preclude potentially curative treatment, limit life expectancy, or both, it is suggested that CT screening should not be performed. (Grade of evidence 2C, indicating a “weak recommendation based on low quality research data”)

Addition of Lung Cancer Screening

Lung cancer is the most important specific cancer risk for Department of Energy (DOE) workers. First, it is a common cancer, representing the second most common site in both men and women in the US. Second, many DOE workers are at increased risk for lung cancer as a result of their occupational exposure to lung carcinogens such as asbestos, beryllium, mercury, radioactive materials, nickel, chlorinated solvents and other chemicals. Third, lung cancer remains an extremely fatal cancer, responsible for the largest percent of all cancer deaths; currently only 15 out of every 100 (15%) of those diagnosed live five years or more. The main reason lung cancer survival statistics are so regretfully low is that most lung cancers are not detected until symptoms appear, at which point cancer has already spread to the lymph nodes or other organs.

Presently, studies are in progress to determine if any screening techniques to detect lung cancer can reduce the death rate from lung cancer. Although lung cancer screening has not to date been proven to reduce mortality, results of medical studies have shown that the chest CT scan may detect lung cancer at an early stage. In late 1999, a landmark study by Cornell University Medical College demonstrated that an effective and feasible method for the early detection of lung cancer was available – low-dose computerized tomography (CT). The study showed that low-dose CT could identify small malignant lung nodules at an early stage, when surgery could successfully remove the cancer, with the potential to cure. All study participants underwent both chest x-ray and a low-dose chest CT scan. The study results were remarkable. The low-dose CT scan detected lung cancer in 27 of 1000 people whereas only 7 lung cancers were detected by chest x-ray. More importantly, low-dose CT scanning nearly always detected lung cancers at an early stage; 85% of the lung cancers detected in the study were early.

The results of the Cornell study, as well as other studies published with similar findings, combined with knowledge of exposures at DOE facilities, led WHPP Director Dr. Steven Markowitz to seek, and successfully secure, funding to offer this innovative and possibly life-saving lung cancer screening method to eligible WHPP participants. The lung cancer screening is offered to workers determined to be at the highest risk for lung cancer as a result of their age, occupational exposures or cigarette smoking history.

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(doi:10.1001/JAMA. 2012.5521. Available pre-embargo to the media at media.jamanetwork.com)

To contact Peter B. Bach, M.D., call Jeanne D’Agostino at 212-639-3573 or email .(JavaScript must be enabled to view this email address).

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